Diterpenoid Alkaloids from Delphinium ajacis and Their Anti-inflammatory Activity.

Three novel diterpenoid alkaloids, comprising two C19 -diterpenoid alkaloids (1 and 2) and one C20 -diterpenoid alkaloid (3), were isolated from Delphinium ajacis, alongside the six known compounds (4-9). Their structures were elucidated by spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and chemical properties. Simultaneously, the anti-inflammatory properties of all compounds (1-9) was conducted, focusing on nitric oxide (NO) production in LPS-induced BV-2 cells. The results indicated compounds 1-3, 7, and 8 have potential anti-inflammatory activity.

Assessment of green roofs' potential to improve the urban thermal environment: The case of Beijing.

Against the backdrop of global warming, rapid urbanization has caused the aggregation of urban building spaces and the heat island effect is becoming increasingly serious, hindering sustainable urban development. In order to investigate the potential and methods of green roofs in different types of neighborhoods to mitigate the urban heat island effect, this study used multivariate data for surface temperature inversion and local climate zone (LCZ), and the potential of green roofs to reduce the heat island effect was evaluated by combining LCZ zoning and ENVI-met prediction model. Finally, a multi-scenario analysis with economic factors was conducted to derive the optimal implementation path for green roofs. The results show that in LCZs 1-9, the green roof can reduce the daytime average air temperature by a maximum of 0.41 °C for 0.5 m of the LCZ8 roof and 0.37 °C for 1.2 m of the LCZ6 pedestrian. Based on the surface cooling efficiency of LCZ green roofs get the best green roof construction order: LCZ3, LCZ6, LCZ8 > LCZ2, LCZ5, LCZ7 > LCZ1, LCZ4, LCZ9. The construction of green roofs for the heat island areas within the fifth ring road of Beijing can reduce the area of high-temperature and sub-high-temperature zones by 52.55% and 29.17%, respectively, compared with the area without green roof construction. The study clarifies the technical methodology system of cooling efficiency of green roofs in different types of neighborhoods and the reduction of the urban-scale heat island effect, which provides a reference for the planning of green roofs for urban buildings.

Lycopodium Alkaloids from Huperzia serrata and Their Anti-acetylcholinesterase Activities.

One new fawcettimine-type alkaloid (1), one new miscellaneous-type alkaloid (2), four new lycodine-type alkaloids (3-6), and eight known ones (7-14) were isolated from the whole plants of Huperzia serrata. Their structures and absolute configurations were elucidated based on spectroscopic data, X-ray diffraction, ECD calculation and Mosher's method. Compound 1 was a rare C18 N2 -type Lycopodium alkaloid, possessing serratinine skeleton with an amide side chain in C-5. The absolute configuration of the 18-OH of compounds 4-6 were first determined by Mosher's method. Moreover, compounds 1-14 were assayed anti-acetylcholinesterase effect in vitro, and compound 7 showed significant anti-acetylcholinesterase activity with an IC50 value of 16.18±1.64 µM.

Proximal femoral bionic nail (PFBN)-an innovative surgical method for unstable femoral intertrochanteric fractures.

PURPOSE: Intertrochanteric femoral fractures (IFF) are one of the most common traumatic conditions, but there are no established treatment methods for this condition due to implant failure and re-operation rates. The proximal femoral bionic nail (PFBN), which is a new design of the cephalomedullary nail, was developed by our team. The objective of this study was to assess the clinical and radiographic outcomes of PFBN in patients with unstable IFF. METHODS: From October 2020 to August 2021, 12 patients diagnosed with unstable IFF (31-A2, 3) were treated with PFBN at the Third Hospital of Hebei Medical University. We evaluated the clinical therapeutic effects of this treatment by measuring peri-operative indicators and post-operative complications. Clinical outcomes, specific radiographic parameters, and post-operative complications were collected and analyzed within the first post-operative year. RESULTS: The average age of the patients was 72.4 ± 16.1 years (five males and seven females). The mean operation time was 90.4 ± 16.0 min, whereas the operation time of 31-A2 fractures (83.1 ± 12.2 min) was shorter than that of 31-A3 fractures (105.0 ± 12.9 min) (p < 0.05). The blood loss was 175 ml (range: 50 to 500 ml), and the length of hospitalization was 10.0 ± 1.9 days. The prognosis evaluation was assessed at three, six and 12 months after the operation; for these time points, the Harris hip scores were 69.6 ± 4.1, 77.8 ± 3.8, and 82.6 ± 4.6, respectively, and the Parker-Palmer scores were 5.3 (5.0, 7.0), 6.3 (5.3, 7.0), and 7.8 (7.0, 8.0), respectively. CONCLUSION: PFBN has shown advantages in the treatment of unstable IFF (particularly in geriatric patients) and possesses both stability and safety. This innovative method may provide a new option for treating unstable IFFs.

Evaluating the Effect of Microcrystalline Cellulose Variations on Tablet Quality of Natural Plant Product Using a Design of Experiment Approach.

Microcrystalline cellulose (MCC) of different grades from different manufacturers differ in particulate and powder properties significantly. The choice of MCC is important to the development of a tablet formulation with satisfactory quality. In this study, the effects of five different MCCs (KG 802, Pharmacel 102, MC 302, M 200, and PH 112) that had different compactibility and tablet disintegration on the tablet quality of two different natural plant products (NPPs) were evaluated systematically, including Crataegi Folium ethanol extract (CF-E) and Sarcandrae Herba water extract (SH-W). The result of D-optimal mixture designs demonstrated that KG 802 showed the best ability to improve compression properties and tensile strength, followed by Pharmacel 102, MC 302, and M 200. PH 112 did the weakest. However, MCCs of different grades had no different influence on the disintegration of NPP tablets. Similar results were found in the experiments of the two different NPP powders, suggesting the generalization of the finding. Moreover, KG 802-containing CF-E formulations showed the largest optimum region size, that is, the lowest production risk. The design space sizes of SH-W were hardly sensitive to the change of MCCs, due to the better tabletability. In conclusion, the properties of MCCs could transfer to the high NPP loading (70%) formulations, leading to the variations on the compression properties and tablet quality. The poorer the tabletability of NPP, the more obvious the variation. The result is promising for the use of MCC and the manufacturing of high drug-loading NPP tablets by direct compression.

[Family analysis of a child with Short-rib polydactyly syndrome type III due to variant of DYNC2H1 gene].

OBJECTIVE: To report on the clinical characteristics of a family of short-rib polydactyly syndrome type III and its pathogenic variants. METHODS: Muscle samples from the the third fetus was collected after the induction of labor, and peripheral blood samples of its parents and grandparents were also collected. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variants were verified by Sanger sequencing of the family. RESULTS: The proband was found to harbor a c.9819+1G>A variant and a c.4625C>A variant of the DYNC2H1 gene, which were respectively inherited from its mother and father. Sanger sequencing verified that the family has fit the autosomal recessive inheritance. CONCLUSION: The c.9819+1G>A and c.4625C>A variants of the DYNC2H1 gene probably underlay the short-rib polydactyly syndrome type 3 in the proband.

Water-soluble matrine-type alkaloids with potential anti-neuroinflammatory activities from the seeds of Sophora alopecuroides.

A phytochemical investigation on the alkaloids from water-soluble part of Sophora alopecuroides led to obtain forty matrine-type alkaloids (1-40) including eighteen new ones (1-18), which covers almost all positions of the oxygen substitution in matrine-type structure. Notably, eight compounds (1-8) belong to rare bis-amide matrine-type alkaloid. The new structures were determined based on extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and six instances, verified by X-ray crystallography. Most of isolates showed anti-neuroinflammatory activities based on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BV2 microglia cells. Especially, compound 39 can suppress those two mediator secretions in a dose-dependent manner with IC50 values of 21.6 ± 0.5 and 16.7 ± 0.8 µM, respectively. Further mechanistic study revealed that 39 suppressed the phosphorylation of IκBα and p65 subunit to regulate the NF-κB signaling pathway.

Clinical research on traditional Chinese medicine treatment for bacterial vaginosis.

Bacterial vaginosis (BV) is a common disease among women of reproductive age, with a serious impact on their daily life and health. At present, the most common treatment for BV is to take antibiotics, which results in good short-term treatment effects, but poor long-term effects. Traditional Chinese medicine (TCM) has been used to treat BV for over a millennium, with little risk of triggering drug resistance and adverse effects. Based on syndrome differentiation, there are three oral TCM treatment strategies for BV, including invigorating spleen, clearing dampness and heat, and nourishing kidney. The oral TCM prescriptions, such as Yi Huang decoction, Longdan Xiegan decoction, Zhibai Dihaung decoction, and so on are commonly used. Topical TCM treatment is also popular in China. According to the research results of pharmacological effects of active TCM ingredients, the most potential mechanisms of TCM for BV treatment are immune-enhancement effects, antibacterial activity, and estrogen-liked effects. Nonetheless, the multi-constituent of herbs may result in possible disadvantages to BV treatment, and the pharmacological mechanisms of TCM need further study. Here, we provide an overview of TCM compounds and their preparations used for BV, based on the pathogenesis and the potential therapeutic mechanisms, therefore providing a reference for further studies.

Erratum: Association of Genes Variants in RANKL/RANK/OPG Signaling Pathway with the Development of Osteonecrosis of the Femoral Head in Chinese Population: Erratum.

[This corrects the article DOI: 10.7150/ijms.19124.].

Association of Genes Variants in RANKL/RANK/OPG Signaling Pathway with the Development of Osteonecrosis of the Femoral Head in Chinese Population.

The RANKL/RANK/OPG pathway plays an important role in regulating bone remodeling and bone turnover. However, the association of the genes variants with the risk of ONFH has rarely been reported. Here, we analyzed the correlation of the 10 SNPs polymorphisms of RANKL, RANK, OPG, TRAF6, and NFATC1 genes with the risk and development of ONFH in 200 ONFH patients and 177 health controls of Chinese population with using Mass ARRAY® platform. The results showed that the recessive model of NFATC1rs9518 was significantly associated with increased ONFH risk (OR:8.223, P=0.048); the proportion of stage Ⅳ patients in the rs9518TC genotype carriers was statistically higher than that of stage Ⅲ patients (P=0.03); in the T-C haplotype carriers of Naftac1, the proportion of bilateral hips lesions was also significantly enhanced than that of unilateral hip lesions(P=0.05). In addition, the proportion of idiopathic ONFH in the TT genotype carriers of OPGrs2073617 was significantly higher than that of steroid or alcohol-induced ONFH, respectively, while in the TC genotype carriers of the SNP, the proportion of idiopathic ONFH remarkably decreased compared with that of Alcohol-induced ONFH, P=0.021. Our results were first found that NFATC1rs9518 closely associated with the risk and the development of ONFH, while OPGrs2073617 statistically correlated with the etiological classification of ONFH.

Dietary diversity and possible cataract among Chinese elderly population.

Background: While cataracts, the vision-clouding eye disease associated with aging, have long presumed dietary underpinnings, the relationship between dietary variety and cataract risk in developing nations has been nebulous. This research aims to investigate the association between dietary diversity scores (DDS) and the risk of cataracts, while considering various dietary diversity patterns. Methods: This research utilized cross-sectional data from 2008 to 2018 extracted from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), implementing the Visual Function Index-14 (VF-14) to gauge cataract probability. The researchers captured participants' diet diversity by using the DDS metric and categorized it into total, animal-based, and plant-based diet patterns. To explore associations between dietary variety and cataract potential, a generalized estimating equation (GEE) was statistically modeled using the data, with adjustments made to account for potentially confounding factors. Additionally, sensitivity analyses were conducted, excluding individuals with assorted eye conditions, to isolate cataract relationships. Results: The study sample comprised 47,395 participants with a mean age of 86.1 years. The study found that a lower likelihood of developing cataract was correlated with both total diet (OR = 0.74; 95% CI: 0.69-0.79) and plant-based diet (OR = 0.65; 95% CI: 0.61-0.71), whereas a slightly higher risk was associated with animal-based diet (OR = 0.90; 95% CI = 0.84-0.96). The results remained unchanged in the sensitivity analysis. Conclusion: The diversified diets are linked to a decreased likelihood of developing cataracts, but animal-based diet faced heightened cataract odds. The implementation of a varied dietary regimen has the potential to serve as a cost-effective and efficient intervention strategy for the prevention of cataracts.

Numerical simulation and tool parameters optimization of aluminum alloy transmission intermediate shell.

Due to its challenging manufacturing and intricate morphology, the aluminum alloy transmission intermediate shell used in vehicle transmission has been the focus of many academic studies. In this study, the three-dimensional cutting model is condensed to a two-dimensional cutting model and utilized to simulate the finishing process of an aluminum alloy workpiece using the finite element modeling program DEFORM-3D. Through orthogonal testing and range analysis, the impact of integral end mill side edge parameters on cutting performance was investigated. It is determined that tool chamfering has a greater impact on cutting performance than tool rake and relief angles, that chamfering width has the most impact on cutting force, and that chamfering angle has the greatest impact on cutting temperature. The workpiece's surface roughness is tested during a cutting experiment, and an analysis of the data reveals that the finite element simulation model is accurate and the orthogonal test method is reasonable. The tool chamfer has a greater impact on roughness than the tool rake angle and relief angle. The tool settings are further optimized using the firefly method. By examining the data, it is determined that the prediction model is correct and the optimization model is reasonable. The cutting efficiency is higher and the surface quality is better when the chamfer width is 0.17 mm and the chamfer angle is 7.3° or 18.3°. Therefore, optimizing the side edge parameters of the integral end mill during the finishing process of a thin-walled aluminum alloy shell has practical technical value.

Lysidrhodosides A-I, acylphloroglucinol glucosides with anti-inflammatory activities from the leaves of Lysidice rhodostegia.

Lysidrhodosides A-I (1-9), nine acylphloroglucinol glucoside derivatives along with three known analogues (10-12) were isolated from the leaves of Lysidice rhodostegia. Their structures and absolute configuration were elucidated by spectroscopic data analysis (NMR, UV, IR, HR-ESI-MS), single-crystal X-ray diffraction, and acid hydrolysis with HPLC analysis. Notably, compounds 7-9 represent the first examples of 3-methylbutyryl phloroglucinol glucoside dimers isolated from this plant. Additionally, compounds 1-12 were assessed for their inhibitory effects on nitric oxide (NO) in the LPS-induced BV-2 cells. The results showed that compounds 6 and 12 significantly inhibited the production of the inflammatory mediator NO, with an inhibitory rate of 95.96 and 91.13% at a concentration of 50 µM, respectively.

Genomic variation in weedy and cultivated broomcorn millet accessions uncovers the genetic architecture of agronomic traits.

Large-scale genomic variations are fundamental resources for crop genetics and breeding. Here we sequenced 1,904 genomes of broomcorn millet to an average of 40× sequencing depth and constructed a comprehensive variation map of weedy and cultivated accessions. Being one of the oldest cultivated crops, broomcorn millet has extremely low nucleotide diversity and remarkably rapid decay of linkage disequilibrium. Genome-wide association studies identified 186 loci for 12 agronomic traits. Many causative candidate genes, such as PmGW8 for grain size and PmLG1 for panicle shape, showed strong selection signatures during domestication. Weedy accessions contained many beneficial variations for the grain traits that are largely lost in cultivated accessions. Weedy and cultivated broomcorn millet have adopted different loci controlling flowering time for regional adaptation in parallel. Our study uncovers the unique population genomic features of broomcorn millet and provides an agronomically important resource for cereal crops.

A county-level study of the effects of state-mandated COVID-19 lockdowns on urban and rural restaurant visits using consumers' cell phone geo-location data.

Aim: US federal, state, and local governments implemented numerous COVID-19 shelter-in-place orders (lockdowns) starting in March 2020 to ensure social distancing regulations and help stop the spread of COVID-19. It is important to know how these lockdowns affected businesses, such as restaurants, in regions that vary in terms of poverty status and geography. In this paper, we analyze the differential changes in rural and urban restaurant visits by the restaurants' NAICS codes following the COVID-19 lockdowns. Our analysis contributes to the public policy literature and helps operational planning for food distribution during a pandemic. Methods: Since urban and rural consumer behavior and food resources are significantly different, it is crucial to conduct a comparative analysis. Our study applies a difference-in-differences model to capture the differential effects lockdowns have on urban and rural restaurants. Results: We find that restaurant visits declined significantly in both rural and urban counties after shelter-at-home orders. The decrease in total restaurant visits was almost twice as high in urban counties as in rural counties. We also find that visits to fast-food restaurants increased in rural counties during shelter-at-home orders. Conclusions: These results contribute to previous studies on the dearth of healthy food in rural and poorer regions, and inform important public policy response in the wake of the COVID-19 pandemic.

Cross-convolutional transformer for automated multi-organs segmentation in a variety of medical images.

Objective.It is a huge challenge for multi-organs segmentation in various medical images based on a consistent algorithm with the development of deep learning methods. We therefore develop a deep learning method based on cross-convolutional transformer for these automated- segmentation to obtain better generalization and accuracy.Approach.We propose a cross-convolutional transformer network (C2Former) to solve the segmentation problem. Specifically, we first redesign a novel cross-convolutional self-attention mechanism in terms of the algorithm to integrate local and global contexts and model long-distance and short-distance dependencies to enhance the semantic feature understanding of images. Then multi-scale feature edge fusion module is proposed to combine the image edge features, which effectively form multi-scale feature streams and establish reliable relational connections in the global context. Finally, we use three different modalities, imaging three different anatomical regions to train and test multi organs and evaluate segmentation performance.Main results.We use the evaluation metrics of Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95) for each dataset. Experiments showed the average DSC of 83.22% and HD95 of 17.55 mm on the Synapse dataset (CT images of abdominal multi-organ), the average DSC of 91.42% and HD95 of 1.06 mm on the ACDC dataset (MRI of cardiac substructures) and the average DSC of 86.78% and HD95 of 16.85 mm on the ISIC 2017 dataset (skin cancer images). In each dataset, our proposed method consistently outperforms the compared networks.Significance.The proposed deep learning network provides a generalized and accurate solution method for multi-organ segmentation in the three different datasets. It has the potential to be applied to a variety of medical datasets for structural segmentation.

Lactose in tablets: Functionality, critical material attributes, applications, modifications and co-processed excipients.

Lactose is one of the most widespread excipients used in the pharmaceutical industry. Because of its water solubility and acceptable flowability, lactose is generally added into tablet formulation to improve wettability and undesirable flowability. Based on Quality by Design, a better understanding of the critical material attributes (CMAs) of raw materials is beneficial in guiding the improvement of tablet quality and the development of lactose. Additionally, the modifications and co-processing of lactose can introduce more-desirable characteristics to the resulting particles. This review focuses on the functionality, CMAs, applications, modifications and co-processing of lactose in tablets.

Association between tea drinking and disability levels in older Chinese adults: a longitudinal analysis.

Objective: As the global population ages, disability among the elderly presents unprecedented challenges for healthcare systems. However, limited research has examined whether dietary interventions like tea consumption may alleviate and prevent disability in older adults. As an important dietary therapy, the health benefits of tea drinking have gained recognition across research disciplines. Therefore, this study aimed to investigate the association between tea drinking habits and disability levels in the elderly Chinese population. Methods: Leveraging data from the 2008 to 2018 waves of the Chinese Longitudinal Healthy Longevity Survey, we disaggregated tea drinking frequency and activities of daily living (ADL) measures and deployed fixed-effect ordered logit models to examine the tea-disability association for the first time. We statistically adjusted for potential confounders and conducted stratified analyses to assess heterogeneity across subpopulations. Results: Multivariable fixed-effect ordered logistic regression suggested tea drinking has protective effects against ADL disability. However, only daily tea drinking was associated with lower risks of basic activities of daily living (BADL) disability [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.41-0.92] and lower levels of instrumental activities of daily living (IADL) disability (OR = 0.78; 95% CI, 0.64-0.95). Stratified analyses indicated heterogeneous effects across age and income groups. Daily tea drinking protected against BADL (OR = 0.26 and OR = 0.28) and IADL disability (OR = 0.48 and OR = 0.45) for adults over 83 years old and high-income households, respectively. Conclusion: We found that drinking tea almost daily was protective against disability in elderly people, warranting further research into optimal dosages. Future studies should utilize more rigorous causal inference methods and control for confounders.

AI approach to biventricular function assessment in cine-MRI: an ultra-small training dataset and multivendor study.

Objective. It was a great challenge to train an excellent and generalized model on an ultra-small data set composed of multi-orientation cardiac cine magnetic resonance imaging (MRI) images. We try to develop a 3D deep learning method based on an ultra-small training data set from muti-orientation cine MRI images and assess its performance of automated biventricular structure segmentation and function assessment in multivendor.Approach. We completed the training and testing of our deep learning networks using only heart datasets of 150 cases (90 cases for training and 60 cases for testing). This datasets were obtained from three different MRI vendors and each subject included two phases of the cardiac cycle and three cine sequences. A 3D deep learning algorithm combining Transformers and U-Net was trained. The performance of the segmentation was evaluated using the Dice metric and Hausdorff distance (HD). Based on this, the manual and automatic results of cardiac function parameters were compared with Pearson correlation, intraclass correlation coefficient (ICC) and Bland-Altman analysis in multivendor.Main results. The results show that the average Dice of 0.92, 0.92, 0.94 and HD95 of 2.50, 1.36, 1.37 for three sequences. The automatic and manual results of seven parameters were excellently correlated with the lowestr2 value of 0.824 and the highest of 0.983. The ICC (0.908-0.989,P< 0.001) showed that the results were highly consistent. Bland-Altman with a 95% limit of agreement showed there was no significant difference except for the difference in RVESV (P= 0.005) and LVM (P< 0.001).Significance. The model had high accuracy in segmentation and excellent correlation and consistency in function assessment. It provides a fast and effective method for studying cardiac MRI and heart disease.

Amplification of oxidative stress with a hyperthermia-enhanced chemodynamic process and MTH1 inhibition for sequential tumor nanocatalytic therapy.

During chemodynamic therapy (CDT), tumor cells can adapt to hydroxyl radical (˙OH) invasion by activating DNA damage repairing mechanisms such as initiating mutt homologue 1 (MTH1) to mitigate oxidation-induced DNA lesions. Therefore, a novel sequential nano-catalytic platform MCTP-FA was developed in which ultrasmall cerium oxide nanoparticle (CeO2 NP) decorated dendritic mesoporous silica NPs (DMSN NPs) were used as the core, and after encapsulation of MTH1 inhibitor TH588, folic acid-functionalized polydopamine (PDA) was coated on the periphery. Once endocytosed into the tumor, CeO2 with multivalent elements (Ce3+/4+) could transform H2O2 into highly toxic ˙OH through a Fenton-like reaction to attack DNA as well as eliminating GSH through a redox reaction to amplify oxidative damage. Meanwhile, controllable release of TH588 hindered the MTH1-mediated damage repair process, further aggravating the oxidative damage of DNA. Thanks to the excellent photothermal performance of the PDA shell in the near-infrared (NIR) region, photothermal therapy (PTT) further improved the catalytic activity of Ce3+/4+. The therapeutic strategy of combining PTT, CDT, GSH-consumption and TH588-mediated amplification of DNA damage endows MCTP-FA with powerful tumor inhibition efficacy both in vitro and in vivo.